Novel Analysis Software for Detecting and Classifying Ca2+ Transient Abnormalities in Stem Cell-Derived...

Area of Science:

• Cardiology
• Biophysics
• Computational Biology

Background:

• Proper calcium (Ca2+) cycling is essential for cardiomyocyte (CM) function and excitation-contraction coupling.
• Abnormal Ca2+ cycling is implicated in arrhythmogenesis, cardiac disorders, and heart failure.
• Induced pluripotent stem cells (iPSC) from patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) exhibit Ca2+ cycling abnormalities.

Purpose of the Study:

• To develop and validate a software tool, AnomalyExplorer, for objective and efficient analysis of cardiomyocyte Ca2+ transients.
• To overcome limitations of manual Ca2+ transient analysis, including low throughput and high variability.
• To facilitate the classification of normal and abnormal Ca2+ transient patterns.

Main Methods:

• Generation of spontaneously beating CMs from iPSC of CPVT patients.
• Development of AnomalyExplorer, a software tool utilizing interactive visualization for Ca2+ transient pattern classification.
• Comparison of AnomalyExplorer's analysis efficiency and consistency against manual analysis.

Main Results:

• AnomalyExplorer effectively detects both normal and abnormal Ca2+ transients in CMs.
• The software provides more defined and consistent information on Ca2+ abnormality patterns and cell line differences compared to manual analysis.
• AnomalyExplorer significantly improves accuracy and reduces user-dependency in Ca2+ transient analysis.

Conclusions:

• AnomalyExplorer is a valuable tool for accurate, efficient, and user-independent analysis of CM Ca2+ transients.
• This software facilitates the study of basic disease pathology, such as in CPVT.
• AnomalyExplorer can accelerate research on the effects of drugs on Ca2+ cycling in cardiac disorders.